Preemptive Therapy For CMV Reactivation in HSCT

Robert J. Soiffer, MD: Over the past 1 to 2 decades, we’ve been treating patients who end up reactivating their CMV infection preemptively. Explain that to me. How frequently? What agents are used, traditionally, when you initiate therapy?

Genovefa Papanicolaou, MD: The preemptive strategy is a very effective method in preventing CMV from going into various organs and causing disease. In this era of very sensitive molecular assays, CMV disease is probably around 5%, depending on their risk. I would say that for the standard risk patients, it’s about 5%. Perhaps, at higher risk, it is even closer to 10%. So, we monitor. Once the patient develops CMV viremia, we start treatment with ganciclovir or the oral form of ganciclovir or valganciclovir (or Valcyte).

Robert J. Soiffer, MD: I know that at our own institution, that’s often quite effective. But there are complications with those agents that make it sometimes difficult to use.

Genovefa Papanicolaou, MD: Right. For some patients that react to CMV quite early, their blood counts are still low and they cannot get ganciclovir in the beginning. We have to use foscarnet, which is given intravenously and carries significant nephrotoxicity. But for the patients that can receive ganciclovir, several of them eventually may develop cytopenias. They may develop a neutropenia, thrombocytopenia. And potentially, we have to either lower the dose of the medication or stop it completely.

Robert J. Soiffer, MD: I know there’s some controversy about the level at which to start preemptive therapy when one gets CMV reactivation. What level do you use at your institution?

Genovefa Papanicolaou, MD: We stratify patients as high risk and low risk. For the patients that are at high risk, we actually start at any detectable CMV viral load, even beyond the level of quantification. In the standard risk population, we probably want to see a couple of consecutive positive viral loads. If we see a trend of rising in about 500 international units, then we start treatment.

Robert J. Soiffer, MD: Right. Obviously, patients who get into trouble with cytopenias are susceptible to other infections, right? They are susceptible to bacterial infections and fungal infections.

Genovefa Papanicolaou, MD: Right.

Robert J. Soiffer, MD: So, it’s not just the CMV, itself, that can cause complications. It can actually be complications from the treatment of the CMV.

Genovefa Papanicolaou, MD: Certainly. Cytopenia is predisposed to, as you mentioned, bacterial infections. So, bacteremia, fungal infections. And even more importantly, CMV has an immunomodulatory effect and creates a greater degree of immunosuppression. Patients may actually be more susceptible to other viral infections. And so, CMV really affects non-relapsed mortality. A number of retrospective cohort studies have demonstrated that CMV-seropositive patients have lower survival rates compared to CMV-seronegative patients. And those patients that had CMV reactivation also have higher mortality rates compared to CMV-seronegative patients.

Transcript Edited for Clarity

Transcript:

Robert J. Soiffer, MD: Over the past 1 to 2 decades, we’ve been treating patients who end up reactivating their CMV infection preemptively. Explain that to me. How frequently? What agents are used, traditionally, when you initiate therapy?

Genovefa Papanicolaou, MD: The preemptive strategy is a very effective method in preventing CMV from going into various organs and causing disease. In this era of very sensitive molecular assays, CMV disease is probably around 5%, depending on their risk. I would say that for the standard risk patients, it’s about 5%. Perhaps, at higher risk, it is even closer to 10%. So, we monitor. Once the patient develops CMV viremia, we start treatment with ganciclovir or the oral form of ganciclovir or valganciclovir (or Valcyte).

Robert J. Soiffer, MD: I know that at our own institution, that’s often quite effective. But there are complications with those agents that make it sometimes difficult to use.

Genovefa Papanicolaou, MD: Right. For some patients that react to CMV quite early, their blood counts are still low and they cannot get ganciclovir in the beginning. We have to use foscarnet, which is given intravenously and carries significant nephrotoxicity. But for the patients that can receive ganciclovir, several of them eventually may develop cytopenias. They may develop a neutropenia, thrombocytopenia. And potentially, we have to either lower the dose of the medication or stop it completely.

Robert J. Soiffer, MD: I know there’s some controversy about the level at which to start preemptive therapy when one gets CMV reactivation. What level do you use at your institution?

Genovefa Papanicolaou, MD: We stratify patients as high risk and low risk. For the patients that are at high risk, we actually start at any detectable CMV viral load, even beyond the level of quantification. In the standard risk population, we probably want to see a couple of consecutive positive viral loads. If we see a trend of rising in about 500 international units, then we start treatment.

Robert J. Soiffer, MD: Right. Obviously, patients who get into trouble with cytopenias are susceptible to other infections, right? They are susceptible to bacterial infections and fungal infections.

Genovefa Papanicolaou, MD: Right.

Robert J. Soiffer, MD: So, it’s not just the CMV, itself, that can cause complications. It can actually be complications from the treatment of the CMV.

Genovefa Papanicolaou, MD: Certainly. Cytopenia is predisposed to, as you mentioned, bacterial infections. So, bacteremia, fungal infections. And even more importantly, CMV has an immunomodulatory effect and creates a greater degree of immunosuppression. Patients may actually be more susceptible to other viral infections. And so, CMV really affects non-relapsed mortality. A number of retrospective cohort studies have demonstrated that CMV-seropositive patients have lower survival rates compared to CMV-seronegative patients. And those patients that had CMV reactivation also have higher mortality rates compared to CMV-seronegative patients.